EXCEED THE SPACE PROVIDED. The Nebraska Center for Virology (NCV), established with an IDeA program award in 2000, links researchers at Nebraska's premiere biomedical research institutions: the University of Nebraska-Lincoln (UNL), the University of Nebraska Medical Center, and Creighton University. In four years we have developed a national presence in virology research and completed our original objectives. The NCV has changed the biomedical research landscape in Nebraska, energizing a shift in the research culture toward inter-disciplinary, thematic, collaborative research and has garnered exceptional institutional support: UNL is constructing a new research building to house all UNL NCV researchers and proposed hires, a commitment that recognizes the central importance of the Center to the university. This competitive continuation proposal details our plan to build the additional capacity that will enable us to achieve our next goal: to become an internationally-recognized independent center of research excellence with diverse but complementary strengths in virology. The NCV will provide an outstanding training environment for the next generation of virologists, further develop collaborative research with private sector partners, and serve as a model of IDeA program success. This goal will be realized by completing three specific aims:1) to further develop our existing faculty through the support of five thematically-linked primary research projects, a strong mentoring program for junior investigators, and support of three critical core facilities; 2) to build the research capacity needed for program project development through targeted recruitment of three researchers in the key areas of viral immunology and molecular virology; and 3) to become a self-sustaining research center through program project funding and increased investigator-initiated grant productivity. The proposed research projects focus on the Pathogenesis of Persistent Infections, studying the molecular mechanisms by which HIV, human papillomavirus, and prions are transmitted, establish persistent infection, interact with the host, and cause disease - with the ultimate goal of contributing to newstrategies to treat and prevent such infections.